癌症疫苗
CTL公司*
CD8型
肽疫苗
T细胞
免疫疗法
癌症免疫疗法
免疫原性
肿瘤抗原
接种疫苗
生物
癌症
黑色素瘤
dna疫苗
抗原提呈细胞
作者
Xuedan He,Shiqi Zhou,Wei-Chiao Huang,Amal Seffouh,Moustafa T. Mabrouk,M Thomas Morgan,Joaquin Ortega,Scott I. Abrams,Jonathan F. Lovell
出处
期刊:ACS Nano
[American Chemical Society]
日期:2021-02-19
卷期号:15 (3): 4357-4371
被引量:12
标识
DOI:10.1021/acsnano.0c07680
摘要
Short major histocompatibility complex (MHC) class I (MHC-I)-restricted peptides contain the minimal biochemical information to induce antigen (Ag)-specific CD8+ cytotoxic T cell responses but are generally ineffective in doing so. To address this, we developed a cobalt-porphyrin (CoPoP) liposome vaccine adjuvant system that induces rapid particleization of conventional, short synthetic MHC-I epitopes, leading to strong cellular immune responses at nanogram dosing. Along with CoPoP (to induce particle formation of peptides), synthetic monophosphoryl lipid A (PHAD) and QS-21 immunostimulatory molecules were included in the liposome bilayer to generate the adjuvant system. In mice, immunization with a short MHC-I-restricted peptide, derived from glycoprotein 70 (gp70), admixed with CPQ safely generated functional, Ag-specific CD8+ T cells, resulting in the rejection of multiple tumor cell lines, with durable immunity. When cobalt was omitted, the otherwise identical peptide and adjuvant components did not result in peptide binding and were incapable of inducing immune responses, demonstrating the importance of stable particle formation. Immunization with the liposomal vaccine was well-tolerated and could control local and metastatic disease in a therapeutic setting. Mechanistic studies showed that particle-based peptides were better taken up by antigen-presenting cells, where they were putatively released within endosomes and phagosomes for display on MHC-I surfaces. On the basis of the potency of the approach, the platform was demonstrated as a tool for in vivo epitope screening of peptide microlibraries comprising a hundred peptides.
科研通智能强力驱动
Strongly Powered by AbleSci AI